The role of antibody glycosylation in autoimmune and alloimmune kidney diseases

Beyze, Anaïs; Larroque, Christian; Le Quintrec, Moglie

doi:10.1038/s41581-024-00850-0

Nat Rev Nephrol

2024

DOI: 10.1038/s41581-024-00850-0

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The role of antibody glycosylation in autoimmune and alloimmune kidney diseases

Anaïs Beyze,

Christian Larroque,

Moglie Le Quintrec

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2024

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Cited by 4 publications

References 320 publications

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The importance of IgG glycosylation—What did we learn after analyzing over 100,000 individuals

Krištić,

Lauc

2024

Immunological Reviews

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SummaryAll four subclasses of immunoglobulin G (IgG) antibodies have glycan structures attached to the protein part of the IgG molecules. Glycans linked to the Fc portion of IgG are found in all IgG antibodies, while about one‐fifth of IgG antibodies in plasma also have glycans attached to the Fab portion of IgG. The IgG3 subclass is characterized by more complex glycosylation compared to other IgG subclasses. In this review, we discuss the significant influence that glycans exert on the structural and functional properties of IgG. We provide a comprehensive overview of how the composition of these glycans can affect IgG's effector functions by modulating its interactions with Fcγ receptors and other molecules such as the C1q component of complement, which in turn influence various immune responses triggered by IgG, including antibody‐dependent cell‐mediated cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC). In addition, the importance of glycans for the efficacy of therapeutics like monoclonal antibodies and intravenous immunoglobulin (IVIg) therapy is discussed. Moreover, we offer insights into IgG glycosylation characteristics and roles derived from general population, disease‐specific, and interventional studies. These studies indicate that IgG glycans are important biomarkers and functional effectors in health and disease.

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The importance of IgG glycosylation—What did we learn after analyzing over 100,000 individuals

Krištić,

Lauc

2024

Immunological Reviews

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The role of autoantibodies in bridging obesity, aging, and immunosenescence

Valentino,

Chen,

Makhijani

et al. 2024

Immun Ageing

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Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity.

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Quality-controlled characterization of a monoclonal antibody specific to an EC5-domain of human desmoglein 3 for pemphigus research

Eming,

Riaz,

Müller

et al. 2024

Front. Immunol.

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BackgroundPemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease caused mainly by IgG autoantibodies (auto-abs) against the cadherin-type adhesion molecules desmoglein (Dsg) 1 and 3. Pathogenic anti-Dsg3 auto-abs bind to different Dsg3 epitopes, leading, among others, to signalling that is involved in pathogenic events, such as Dsg3 depletion. As central tools in research on PV, a limited number of antibodies such as AK23 are frequently used by the autoimmune bullous disease community.MethodsPreviously, we have introduced a novel Dsg3 EC5-binding antibody termed 2G4 that may potentially serve as a superior tool for numerous PV related analysis. The purpose of this study was to develop a quality-controlled production and verification process that allows I) a continuous quality improvement, and II) a verified and comprehensible overall quality with regard to pathogenic antigen-specific binding in a variety of pemphigus assays for each batch production.ResultsThus, a workflow based on a standardized operating procedure was established. This includes the verification of purity and in-vitro binding capacity (SDS-page, direct and indirect immunofluorescence) as primary parameters, and size analysis by mass-spectrometry and ex-vivo pathogenicity by monolayer dissociation assay.ConclusionWe here present an extensive point-by-point quality controlled IgG production protocol, which will serve as a basis for a standardized antibody assessment in PV research.

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The role of antibody glycosylation in autoimmune and alloimmune kidney diseases

Cited by 4 publications

References 320 publications

The importance of IgG glycosylation—What did we learn after analyzing over 100,000 individuals

The importance of IgG glycosylation—What did we learn after analyzing over 100,000 individuals

The role of autoantibodies in bridging obesity, aging, and immunosenescence

Quality-controlled characterization of a monoclonal antibody specific to an EC5-domain of human desmoglein 3 for pemphigus research

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